Stimuli-Responsive MOF Nanocarriers for Precision Pulmonary Delivery of Aloperine in Acute Lung Injury

Acute lung injury (ALI), known as a severe respiratory disease, often leads to increased inflammation, harm to the alveolar-capillary barrier, and decreased oxygenation, with high morbidity and mortality rates. Herein, we study aloperine (ALO), a hydrophobic anti-inflammatory alkaloid with traditional Chinese medicine origins for ALI treatment. Importantly, effective ALO encapsulation is made possible over a zirconium-based UiO-66-NH₂ metal-organic framework nanocarrier, which is renowned for its enormous surface area, structural stability, and adjustable porosity. In vitro release showed pH-responsive ALO due to protonation-induced disruption of Zr ligands. Ex vivo imaging showed rapid lung deposition, peaking at 12 h and persisting for up to 24 h with minimal off-target distribution. In an LPS-induced ALI mouse model, nebulized ALO@F127-MOF significantly improved oxygenation, reduced inflammatory cell infiltration, pulmonary edema, and pro-inflammatory cytokines (TNF-α, IL-6) in bronchoalveolar lavage fluid. Notably, effective outcomes were achieved using a very low quantity compared to the standard drug dose, underscoring its targeted therapeutic potential as an effective pulmonary delivery system for drugs for inflammatory lung disease. This study establishes a rational MOF-based nanoplatform for precision pulmonary delivery of anti-inflammatory agents, offering a promising avenue for ALI and related inflammatory lung diseases.